Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology

Taresco, Vincenzo; Louzao, Iria; Scurr, David J.; Turpin, Eleanor R.; Laughton, Charles A.; Alexander, Cameron; Burley, Jonathan C.; Garnett, Martin

Abstract

A miniaturized, high-throughput assay was optimized to screen polymer-drug solid dispersions using a 2-D Ink-jet printer. By simply printing nanoliter amounts of polymer and drug solutions onto an inert surface, drug:polymer micro-dots of tunable composition were produced in an easily-addressable micro-array format. The amount of material printed for each dried spot ranged from 25 ng to 650 ng. These arrays were used to assess the stability of drug:polymer dispersions with respect to recrystallization, using polarized light microscopy. One array with a panel of 6 drugs formulated at different ratios with Poly (vinylpyrrolidone-vinyl acetate) copolymer (PVPVA) was developed to estimate a possible bulk (gram-scale) approximation threshold from the final printed nano amount of formulation. Another array was printed at a fixed final amount of material to establish a literature comparison of one drug formulated with different commercial polymers for validation. This new approach may offer significant efficiency in pharmaceutical formulation screening, with each experiment in the nano-micro-array format requiring from 3 up to 6 orders of magnitude lower amounts of sample than conventional screening methods.

Citation

Taresco, V., Louzao, I., Scurr, D. J., Turpin, E. R., Laughton, C. A., Alexander, C., Burley, J. C., & Garnett, M. (in press). Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology. Molecular Pharmaceutics, 14(6), https://doi.org/10.1021/acs.molpharmaceut.7b00182

• Journal Article Type: Article
• Acceptance Date: May 14, 2017
• Online Publication Date: May 14, 2017
• Deposit Date: May 17, 2017
• Publicly Available Date: May 17, 2017
• Journal: Molecular Pharmaceutics
• Print ISSN: 1543-8384
• Electronic ISSN: 1543-8392
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 6
• DOI: https://doi.org/10.1021/acs.molpharmaceut.7b00182
• Keywords: High throughput array, Ink-jet printing, Amorphous dispersion, Recrystallisation, Polarizing microscopy
• Public URL: https://nottingham-repository.worktribe.com/output/860398
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00182
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters copyright © 2017 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00182
• Contract Date: May 17, 2017